The onset of postoperative complications due to infections at surgical sites is a problem when surgical operations are performed. Postoperative infections are classified into surgical site infections (SSI) and remote infections such as pneumonia or urinary tract infections. Surgical site infections mean infections that take place at sites directly subjected to operations. Remote infections mean infections that take place at sites not directly subjected to operations. Furthermore, SSI is further classified as incisional SSI and organ/space SSI. Incisional SSI includes superficial incisional SSI, the onset sites of which are limited to the skin and subcutaneous tissues, and deep incisional SSI, which reaches deeper soft tissues. Furthermore, organ/space SSI means infections of any organs or sites other than incisions that have been subjected to surgical operation (Takashi Yokoyama et al: Prevention of Surgical Site Infection (SSI), Emergency and Intensive Care (Kyukyu/Shuchuchiryo) vol. 14 no. 6 2002(6): 637-644).
Regarding etiologic bacteria of these infections, the onset of a surgical site infection is caused by contaminants that exist in the operative fields and are resistant to administered antimicrobial agents. It is generally said that the onset of a remote infection is often caused by antibiotic-resistant bacteria that cause nosocomial infections, such as Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA). To prevent postoperative infections and, in particular surgical site infections, a chemotherapeutic drug such as an antibiotic is generally administered for prevention purpose. An important point in this case in terms of prevention of postoperative infections is the targeting of bacteria that can cause intraoperative contamination; that is, indigenous bacteria and contaminants in the operative fields or bacteria that are isolated from resection stumps. Normal bacterial flora significantly differs from organ to organ. The number of bacteria in the upper gastrointestinal tract is generally as few as approximately 105/g because of the effect of gastric hydrochloric acid, while the number of bacteria in the lower digestive tract reaches as high as 1011 to 1012/g. Moreover, bacterial species also vary significantly. Gram-positive cocci are the dominant bacterial species in the upper gastrointestinal tract or the respiratory system. Gram-negative bacteria and anaerobic bacteria such as Bacteroides and Lactobacillus bifidus are the dominant bacterial species in the intestine (Yoshinobu Sumiyama and Yohichi Arima: Preventive Administration of Antimicrobial Agent upon Operation, Emergency and Intensive Care (Kyukyu/Shuchu Chiryo) vol. 14, No. 6, 2002(6): 645-650). Therefore, for surgery of the lower digestive tract, for example, drugs such as cephems of the 2nd and following generations, which have wide-ranging antibacterial spectra, carbapenem antibiotics, and new quinolone antibiotics are used.
The occurrence frequencies of SSI that occurs after operations on the digestive system, and specifically, of incisional SSI, are extremely high. Inflammatory bowel disease (IBD) is a disease that is treated by operation on the digestive system. Examples of such disease include ulcerative colitis (UC), Crohn's disease (CD), as well as infectious colitis, drug induced colitis, ischemic colitis, radiation colitis, intestinal tuberculosis, and intestinal syphilis. Of these, ulcerative colitis (UC) and Crohn's disease (CD) cases are increasing yearly and are distinguished from other disease cases in view of the frequency of their occurrence.
Ulcerative colitis (UC) is cryptogenic inflammation of the large intestine. Ulcerative colitis is also a diffuse non-specific inflammatory disease that occurs mainly in the large intestine and specifically occurs only between the rectum and the cecum, and it is characterized by continuous lesions. The development sites of such inflammations are limited to mucosa and stratum submucosum. Furthermore, UC is characterized by repeated remission and exacerbation and absence of complete cure.
Regarding ulcerative colitis (UC), elucidation of the amplification mechanism of the inflammation, development of therapeutic methods based on the findings from the elucidation, and development of therapeutic agents for UC are currently being aggressively carried out. For example, leukocyte apheresis (LCAP) using CELLSORBA™, granulocyte apheresis (GCAP) using ADACOLUMN™, or leukocyte apheresis based on centrifugation using an apparatus for collecting blood components has been proven to be effective and is thus recognized as a therapeutic method that is covered by insurance. Furthermore, clinical development tests of anti-CD4 antibodies, anti-TNF-α antibodies, or the like is in progress. However, at actual clinical sites, ulcerative colitis is treated mainly through administration of sulfasalazine (trade name: salazopyrin), which is a sulfa drug and has long been used, RINDERON™ (suppository), or a steroid drug. UC is treated by a combination of such drug administration, nutritional control, psychiatric control, and the like. If such treatment is still ineffective, surgical therapy (surgical operation) is further performed in general.
As described above, the fact that operation on the digestive system often results in the onset of postoperative complications is acknowledged as a problem. For example, the development status of SSI in the past 3 years and 10 months was examined at the medical institution to which the present inventors belong. As a result, the incidence rate of SSI was approximately 20% in the case of operations for gastric cancer, approximately 30% in the case of operations for large bowel cancer, and approximately 33% in the case of operations for rectal cancer, while the incidence rate of SSI was as high as approximately 60% in the case of operations for inflammatory bowel disease including ulcerative colitis.
This may be due to the involvement of immunosuppression status resulting from administration of large amounts of steroids and abnormal conditions resulting from the morbidity of the disease, such as systemic inflammatory response syndrome (SIRS). Actually, when the relationships between the doses of steroids and the incidence rates of postoperative complications were examined, whereas the incidence rate of complications was as high as 65% in the case of a total steroid dose of 7,000 mg or more, the same was approximately only 28% in the case of a total steroid dose of 7,000 mg or less. Moreover, total steroid doses were contrasted with the incidence rates of SSI in the cases of operations for ulcerative colitis. As a result, SSI onset was confirmed at a high level when the total steroid dose administered was more than approximately 15,000 mg, but a significantly low level of SSI onset was confirmed when the same was less than 8,000 mg.